Oxidative rearrangement of malondialdehyde: substrate scope and mechanistic insights

Abstract

Interception of Criegee intermediate via tandem acetalization and fragmentation reaction provides a novel oxidative decarbonylation of malondialdehyde.

Stereospecific Construction of Contiguous Quaternary All‐Carbon Centers by Oxidative Ring Contraction

“…In line with our recent work on oxidative deformylation reactions, we envisioned that the α‐formyl cyclic ketone 3 could condense with H 2 O 2 to generate the Criegee intermediate 4 , which would lead to the 1,2‐dioxolane A by intramolecular cyclization (Figure b) . Subsequently, A would be involved in fragmentation by two distinct reaction pathways.…”

“…At the outset, cyclic α‐formyl ketones ( 3 ) bearing various substituents adjacent to the carbonyl group were prepared and evaluated under our previously developed oxidative deformylation conditions (Table ) . The ketone 3 a , without any substituent at C1, was fully recovered (entry 1).…”

Stereospecific Construction of Contiguous Quaternary All‐Carbon Centers by Oxidative Ring Contraction

“…In line with our recent work on oxidative deformylation reactions, [9] we envisioned that the a-formyl cyclic ketone 3 could condense with H 2 O 2 to generate the Criegee intermediate 4,w hich would lead to the 1,2-dioxolane A by intramolecular cyclization ( Figure 2b). [9,10] Subsequently, A would be involved in fragmentation by two distinct reaction pathways.M igration of alkyl substituents (path a) would deliver the ring-contraction product 5 and shift of the hydride (path b) would provide the bis(carboxylic acid) 6 by CÀC bond cleavage. [10] Herein, we report that the fragmentation of A could be biased toward path ab yj udiciously introducing substituents to the a-carbon atoms of cyclic ketones,and thus pave an efficient way for stereospecifically forging contiguous quaternary all-carbon centers.…”

“…At the outset, cyclic a-formyl ketones (3)bearing various substituents adjacent to the carbonyl group were prepared and evaluated under our previously developed oxidative deformylation conditions (Table 1). [9] Theketone 3a,without any substituent at C1, was fully recovered (entry 1). The introduction of am ethyl group at C1 led to complete conversion of the ketone 3b,t hus producing the acid 5b in 64 %yield together with the bis(carboxylic acid) 6b in aratio of 1.8:1 (entry 2).…”

Mechanism and Selectivity of the Oxidative Ring Contraction of Cyclic α‐Formyl Ketones

“…The a-formyl cyclic ketonei nteracts with one H 2 O 2 throught wo hydrogen bonds, followed by reaction with another H 2 O 2 molecule to form the Criegee intermediate INT2,which couldthen proceed through an intramolecular isomerization to generate INT3.R eleasingo fo ne H 2 O 2 and simultaneously intramolecular cyclization leads to the 1,2-dioxolane intermediate INT4. [6] Subsequently, INT4 could lead to two distinct reaction pathways. Migration of alkyl substituents (through TS4)w ould deliver the ring-contraction product while shift of the hydride (through TS5)w ould provide the biscarboxylic acid by CÀCb ond cleavage.…”